This invention relates to ocular treatment devices, and particularly to a device of the kind which is operable to deliver to the eye treatment fluids in the form of a jet and/or small droplets.
Ophthalmic treatment fluids are commonly administered to the eye by means of eye drops or ointments. The use of eye drops has a number of disadvantages, primarily as a consequence of the difficulty with which drops are accepted by the patient. The drops are relatively large, and the instinctive blink that is provoked by the arrival of a drop on the eye severely limits the amount of or proportion of fluid that actually contacts the target area on the eye. Typically less than 10% of a 50 xcexcl drop can be effective, the remainder being lost by drainage, either externally or through nasolacrimal drainage. Such use of expensive treatment fluids is wasteful, as well as leading to substantial uncertainty regarding the effectiveness of a treatment. Similar comments apply to the use of ointments, although levels of wastage can be reduced by careful delivery. The greater viscosity of ointments reduces their tendency to drain or be washed away.
In our International Patent Application No. PCT/GB95/01482 there are proposed various techniques for delivering treatment fluid to the eye. These employ systems in which treatment fluid is drawn from a reservoir and discharged in a controlled manner to the eye. While these techniques are useful, there are difficulties arising from the repeated use of the multi-dose nozzle. Specifically, it is difficult to maintain the sterility of the treatment fluid in a system in which doses of fluid are successively drawn from a reservoir, and passed through a re-usable nozzle without the use of preservatives. The use of preservatives has caused some concern as discussed on pages 8-11 of xe2x80x9cOphthalmic Drug Delivery Systemsxe2x80x9d (Drugs in the Pharmaceutical Sciences, Volume 58), published in 1993 by Marcel Dekker.
Reference is also directed to U.S. Pat. No. 3,934,585 which discloses a variety of mechanisms for delivering unit doses of treatment fluid to the human eye. The doses are held in dispensing tubes which are fitted in the mechanisms when treatment is required. The mechanisms are operative to apply compressed air to one end of a tube resulting in the discharge of treatment fluid from the other end.
It is an aim of the present invention to minimise or eliminate the need to use preservatives in ophthalmic treatment fluids without risking contamination. Thus, in a primary aspect, the present invention provides a unit container for a treatment fluid comprising a sealed enclosure of which one wall section thereof is formed with at least one opening, the enclosure being pressuriseable to discharge its contents through said at least one opening, which opening is of sufficient diameter to enable the generation of a jet and/or discrete droplets of treatment fluid discharged therefrom.
The wall section of a container according to the invention formed with the opening or openings is typically a flat section of the enclosure wall, and the enclosure is typically a blister pack, with the wall section at a planar base of the blister. However, we have found that some particular benefits arise from the adoption of a non-planar wall section in which the opening or openings are formed. More particularly, we have found that the adoption of a dome shape in the respective wall section can result in a more reliable performance of the containers in use, and facilitate certain other beneficial developments of the containers. Thus, in preferred embodiments of the invention, a unit container for a treatment fluid comprising an enclosure of which one wall section is dome shaped and formed with at least one opening in the top region of the dome shape, the enclosure being adapted to confine a sealed volume of treatment fluid, and pressurisable to discharge the contents of the sealed volume through said at least one opening. One or more other wall sections may also define a dome shape complementary to that with the opening, which is capable of inversion into the one wall section in the discharge of the container contents.
The enclosure of a unit container of the invention can be pressurised by the application of an external force on the side of the enclosure opposite the wall section formed with the opening or openings. Where the respective wall section is substantially flat, this method of pressurising the enclosure contents can create high stresses in the wall section, and particularly around the opening or openings. In some situations, this can result in the wall section itself tearing around the opening or openings with the consequence that the discharge of the enclosure contents becomes less predictable. By locating the opening or openings at the top of a dome shape, these stresses are reduced.
Either a single opening or an array of openings may be found in the respective wall section of the container. Various arrays are possible, and a particular choice will be influenced by a number of factors. A larger number of openings will dispense treatment fluid over a larger target area. Smaller openings produce narrower jets and/or smaller drops which will be subject to greater deceleration in their passage to the target area. This may allow the use of higher pressures. A single opening can direct a jet or stream of drops accurately to a specific target area, and minimise the time taken to deliver the treatment fluid to beat the blink response. The preferred minimum opening diameter is at least 10 xcexcm to avoid creating a spray of droplets with insufficient linear momentum to reach their target. The use of a single opening of 100 xcexcm diameter is particularly preferred. The intention is to create droplets no smaller than say 20 xcexcm to avoid the creation of an inhalable spray.
Another-benefit arising from the adoption of a dome shaped wall section in which the opening or openings are defined is that discharge of substantially the entire contents of the enclosure is facilitated. If the device used to pressurise the enclosure is a piston or hammer, its operative end can be shaped to complement that of the dome such that in operation the other wall sections of the enclosure, which can similarly be shaped to complement that of the dome, are inverted against the dome shaped wall section thus substantially evacuating the entire enclosure.
The wall section of the enclosure in a container of the invention may be provided with a removable cover overlaying the opening or openings, which cover is only removed just prior to the contents of the enclosure being discharged. In this way, the contents are protected from the environment until required. In an alternative arrangement the or each opening in the wall section of the enclosure is closed by a membrane adapted to rupture upon pressurisation of the enclosure. These means demonstrate how treatment fluids can be kept sterile in containers of the invention. As a consequence, the need for the use of preservatives in the contents is minimised or eliminated.
The use of a dome wall section in preferred containers of the present invention facilitates the creation of a separate sealed volume within the enclosure. In these circumstances, the removable cover overlaying the opening or openings can be dispensed with, or at least the requirements for its sealing qualities can be reduced. According to this aspect of the invention, which can of course also be applied to a container without a dome shaped wall section with the opening or openings, a dividing wall is included within the enclosure, which dividing wall separates the wall section with the opening or openings from a region within the enclosure which defines the sealed volume. The dividing wall is adapted to rupture prior to discharge of the contents from the enclosure. Conveniently, the dividing wall can be adapted to rupture upon pressurisation of the enclosure as part of the step of discharging the contents of the sealed volume through the opening or openings in the wall section. However, the dividing wall may be adapted to rupture upon the application of an external force prior to pressurisation of the enclosure. Particularly, when the container is fitted, either as an individual unit or as part of a strip for example, in a dispensing device, a mechanism can be included to apply tensile force across the container to break the dividing wall just prior to the enclosure being pressurised.
Where a container according to the invention defines a sealed volume with a dividing wall, it will be understood that this sealed volume can be formed as a individual component of the container prior to attachment of the wall section formed with the opening or openings. This feature also offers a number of particular benefits, primarily in the manufacture of packages containing a plurality of complete containers. Manufacturing these components individually means they can be separately checked for defects prior to incorporation in d package. It also facilitates the creation of packages having containers with different dosages; either different treatment fluids or different quantities of the same fluid, and also enables a plurality of individual components to be disposed under a common dome shaped wall section, whereby different treatment fluids can be kept isolated, but mixed just prior to discharge from the opening or openings.
Containers of the invention are designed to provide for the successive or simultaneous delivery of a jet or small droplets, sometimes in the form of a stream or spray, which may be diffuse or collinear. A typical range for the size of opening in the wall section of the enclosure to achieve is up to 1000 xcexcm, preferably 20 to 200 xcexcm. A particularly preferred size range is 100 to 150 xcexcm. A single opening or an array of openings can be used, conveniently punched, drilled, electroformed or laser-drilled in a plastics sheet or foil defining the wall section. A metal, typically a nickel foil is preferred for electroforming.
The form of delivery that is appropriate for a particular ophthalmic treatment; ie, single or multiple openings, and the arrangement thereof, will be dictated by the need to achieve a sufficient delivery rate to beat the xe2x80x9cblink responsexe2x80x9d, with minimal adverse reaction or unpleasant sensation to the eye. Thus, if a higher quantity of fluid must be delivered, in order to ensure delivery prior to the patient blinking, and at a tolerable impact speed, multiple openings will be used instead of a single opening to achieve a sufficient overall delivery rate.
Unit containers according to the invention can be charged such that each enclosure confines a prescribed unit dose for discharge therefrom, typically no more than 10 xcexcl. However, larger volumes such as 20, 50 or 100 xcexcl could be required, for example for irrigation purposes. A plurality of containers may be provided in the form of a package, conveniently on a common substrate, and preferably in the form of a strip with the containers arranged sequentially therealong.
The discharge of the contents of enclosures in containers according to the invention can most simply be accomplished by provoking the collapse of the enclosure wall, against the section having the opening or openings, preferably by a mechanical system. The wall may include a reinforced region to orient its collapse. For example, the enclosure might be crushed from the side opposite the wall section by a piston, hammer or cantilever mechanism, the action of which may be dampened to control the speed of the mechanism, with sufficient impact to discharge and project the contents a predetermined minimum distance. In an alternative, the enclosure might be formed as a cylindrical chamber, with an opposite wall portion formed as a piston for movement towards the wall section to force the enclosure contents through the opening or openings.
The invention is also directed at devices for discharging a treatment fluid from the sealed enclosures of containers of the type described above. Such a device comprises a package of the containers; a mechanism for feeding the containers seriatim to a dosing station; and means for acting on the enclosure of a container at the dosing station to discharge the contents thereof. The invention also provides a manual feed device in which provision is made for individual containers or packages thereof to be fed manually to the dosing station as required. When the wall section of the container enclosure has a cover, the device can include means for its removal prior to discharge of the enclosure contents. This means may be synchronised with the feeding mechanism.
The discharge of the contents of the enclosure at the dosing station in the above device is preferably accomplished by pressure such that it is forced through the opening or openings in the respective wall section of the enclosure. However, in an alternative, an electrostatic technique can-be used, broadly of the kind described in published European Patent Specification No. 0 224 352. For this alternative, the invention provides a modified unit container in which the enclosure is not specifically pressurisable, but has a wall which includes a conductive section for connection to a source of electrical potential, whereby application of such potential generates an electrical charge in the container contents, and its discharge through said at least one opening.
In discharging devices of the invention in which the discharge of the container contents is accomplished by pressurising its enclosure, the preferred means is a physical mechanism such as a crushing unit for acting directly on the outside of the enclosure from the side opposite the wall section formed with the opening or openings. This can take the form of a piston-cylinder mechanism, and such a mechanism can also be used to move an opposite wall portion in a cylindrical enclosure of the kind described above.
Another technique that can be used to pressurise the enclosure in containers of the invention uses piezoelectric elements. Such elements enable the degree of pressurisation achieved to be accurately controlled, and can be disposed for example, against a face of the enclosure opposite the wall section, or in the form of a ring around the body of the enclosure. In either arrangement such an element can be operated selectively or repeatedly to discharge discrete droplets or a rapid sequence. The element may take the form of an ultrasonic transducer, one which is particularly suited to the generation of a spray through an array of openings in the wall section of the enclosure.
Other features can also be employed in devices according to the invention to indicate the successful delivery of a treatment fluid to its target. A light can be provided to maintain the eye open, and this could typically be white. Alternatively, a coloured system may be employed in which a different colour indicates the stage of treatment. For example, the device can be offered up to the eye showing a red light, which will switch to green only after the predetermined dose has been dispatched.
Devices according to the invention can also include a number of safety features which are already well established in dosing devices of various kinds. The number of containers in a device will of course be finite, and a dose recorder may be included to provide an indication of the number of doses remaining or delivered. A delay mechanism can also be included to prevent the inadvertent delivery of a multiple dose. In combination with the delivery signal features referred to above, this can be of significant benefit.
It will be recognised that devices according to the invention can be for personal or hand held use, or for use on a more regular basis in institutions. For whatever use, means can be provided for ensuring a proper spacing between the device and the eye to be targeted, and this can be made adjustable, particularly in the devices adapted for institutional use. In this respect, it will be noted that the mechanisms contemplated in the present invention will be well capable of discharging a jet and/or droplets substantially horizontally or vertically upwards over a minimum distance, thereby not requiring a user to arrange for the device to be operated from directly above an eye.
In addition to the containers and devices discussed above, the present invention also provides methods of generating jets and/or droplets and of treatment, using such containers and devices. The methods of treatment additionally require the targeting of generated jets and/or droplets at a respective treatment site.